George Molly S, Sanchez Jenifer, Rollings Christina, Fear David, Irving Peter, Sinclair Linda V, Schurich Anna
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK.
Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Scotland DD1 5EH, UK.
iScience. 2023 Jul 4;26(8):107280. doi: 10.1016/j.isci.2023.107280. eCollection 2023 Aug 18.
Long-term T cell dysregulation has been reported following COVID-19 disease. Prolonged T cell activation is associated with disease severity and may be implicated in producing long-covid symptoms. Here, we assess the role of extracellular vesicles (EV) in regulating T cell function over several weeks post COVID-19 disease. We find that alterations in cellular origin and protein content of EV in COVID-19 convalescence are linked to initial disease severity. We demonstrate that convalescent donor-derived EV can alter the function and metabolic rewiring of CD4 and CD8 T cells. Of note, EV following mild, but not severe disease, show distinctly immune-suppressive properties, reducing T cell effector cytokine production and glucose metabolism. Mechanistically our data indicate the involvement of EV-surface ICAM-1 in facilitating EV-T cell interaction. Our data demonstrate that circulatory EV are phenotypically and functionally altered several weeks following acute infection, suggesting a role for EV as long-term immune modulators.
据报道，新冠病毒疾病（COVID-19）后会出现长期的T细胞失调。T细胞的长期激活与疾病严重程度相关，可能与产生长期新冠症状有关。在此，我们评估了细胞外囊泡（EV）在新冠病毒疾病后数周内调节T细胞功能中的作用。我们发现，新冠康复期EV的细胞来源和蛋白质含量的改变与初始疾病严重程度有关。我们证明，康复期供体来源的EV可改变CD4和CD8 T细胞的功能和代谢重塑。值得注意的是，轻症而非重症疾病后的EV表现出明显的免疫抑制特性，可减少T细胞效应细胞因子的产生和葡萄糖代谢。从机制上讲，我们的数据表明EV表面的细胞间黏附分子-1（ICAM-1）参与促进EV与T细胞的相互作用。我们的数据表明，急性感染数周后循环EV在表型和功能上发生了改变，提示EV作为长期免疫调节剂发挥作用。
